Noncoding Functions Research Articles

Poly(A)-Specific Ribonuclease Deficiency Leads to Deregulated Expression of Genes Involved in Sex Determination and Gonadal Maturation in Zebrafish

Abstract Background Deadenylation, the process of removal of poly (A) tail of messenger ribonucleic acids (mRNAs), is a rate-limiting step in mRNA stability, and poly(A)-specific ribonuclease (PARN) is the most important exonuclease involved in this process. Besides mRNA stability, PARN is also involved in several other processes including telomere maintenance, noncoding RNA maturation, ribosome biogenesis, and TP53 function. Previously, we have shown that zebrafish PARN null mutants are viable and fertile but turn out to only develop into males, indicating a role in oogenesis. The present study was focused on analyzing the expression of genes involved in sex determination and gonadal development in PARN mutant zebrafish. Materials and Methods Total RNA was extracted and quantitative real-time polymerase chain reaction was performed to determine the expression level of genes involved in gonad development in PARN mutant embryos (4 days postfertilization [dpf]) and adults (120 dpf) in comparison to their wild-type siblings. The expression levels were estimated by the ΔΔCT relative quantification method. Results At 4 dpf, the expression of germ cell-specific genes did not show any significant difference in the null mutants compared to the heterozygous and their wild-type siblings, suggesting no effect on germ cell differentiation due to the loss of PARN. However, the majority of the ovary-associated genes analyzed showed an increased expression in PARN null and heterozygous mutants compared to the wild-type siblings. Intriguingly, the expression of testis-associated genes showed decreased expression in the mutants compared to their wild-type siblings at 4 dpf. In adult stages, as expected, the expression of genes that jointly regulate the proper formation and function of ovaries and testes showed decreased expression in PARN null mutants. Interestingly, the expression of genes involved in the differentiation of testes, despite showing a decreased expression in the mutants, was comparable between the null and heterozygous mutants. Conclusion Taken together, these results suggest that the loss of PARN does not affect germ cell differentiation but affects the sexual differentiation that happens at later stages of development, particularly the process of oogenesis, in zebrafish.

Epigenome editing technologies for discovery and medicine.

Epigenome editing has rapidly evolved in recent years, with diverse applications that include elucidating gene regulation mechanisms, annotating coding and noncoding genome functions and programming cell state and lineage specification. Importantly, given the ubiquitous role of epigenetics in complex phenotypes, epigenome editing has unique potential to impact a broad spectrum of diseases. By leveraging powerful DNA-targeting technologies, such as CRISPR, epigenome editing exploits the heritable and reversible mechanisms of epigenetics to alter gene expression without introducing DNA breaks, inducing DNA damage or relying on DNA repair pathways.

Tissue-specific enhancer-gene maps from multimodal single-cell data identify causal disease alleles.

Translating genome-wide association study (GWAS) loci into causal variants and genes requires accurate cell-type-specific enhancer-gene maps from disease-relevant tissues. Building enhancer-gene maps is essential but challenging with current experimental methods in primary human tissues. Here we developed a nonparametric statistical method, SCENT (single-cell enhancer target gene mapping), that models association between enhancer chromatin accessibility and gene expression in single-cell or nucleus multimodal RNA sequencing and ATAC sequencing data. We applied SCENT to 9 multimodal datasets including >120,000 single cells or nuclei and created 23 cell-type-specific enhancer-gene maps. These maps were highly enriched for causal variants in expression quantitative loci and GWAS for 1,143 diseases and traits. We identified likely causal genes for both common and rare diseases and linked somatic mutation hotspots to target genes. We demonstrate that application of SCENT to multimodal data from disease-relevant human tissue enables the scalable construction of accurate cell-type-specific enhancer-gene maps, essential for defining noncoding variant function.

RNA-mediated symmetry breaking enables singular olfactory receptor choice

Olfactory receptor (OR) choice provides an extreme example of allelic competition for transcriptional dominance, where every olfactory neuron stably transcribes one of approximately 2,000 or more OR alleles1,2. OR gene choice is mediated by a multichromosomal enhancer hub that activates transcription at a single OR3,4, followed by OR-translation-dependent feedback that stabilizes this choice5,6. Here, using single-cell genomics, we show formation of many competing hubs with variable enhancer composition, only one of which retains euchromatic features and transcriptional competence. Furthermore, we provide evidence that OR transcription recruits enhancers and reinforces enhancer hub activity locally, whereas OR RNA inhibits transcription of competing ORs over distance, promoting transition to transcriptional singularity. Whereas OR transcription is sufficient to break the symmetry between equipotent enhancer hubs, OR translation stabilizes transcription at the prevailing hub, indicating that there may be sequential non-coding and coding mechanisms that are implemented by OR alleles for transcriptional prevalence. We propose that coding OR mRNAs possess non-coding functions that influence nuclear architecture, enhance their own transcription and inhibit transcription from their competitors, with generalizable implications for probabilistic cell fate decisions.

LncRNA LINC01339 Hinders the Development of Wilms' Tumor via MiR-135b-3p/ADH1C Axis.

Wilms' tumor is a malignant renal cancer that arises within the pediatric urinary system. This study intended to investigate how a novel long non-coding RNA LINC01339 functions in the pathogenesis of Wilms' tumor. An elevated miR-135b-3p expression as well as reduced levels of LINC01339 and ADH1C were observed in Wilms' tumor. LINC01339 mediated ADH1C expression by directly binding to miR-135b-3p. The enforced LINC01339 or ADH1C markedly hindered cell growth and migration in Wilms' tumor. The LINC01339 overexpression also repressed the growth of Wilms' tumors in vivo, whereas miR-135b-3p overexpression exerted the opposite effects on Wilms' tumor cells in vitro. Additionally, upregulating miR-135b-3p reversed LINC01339's effects on the cellular processes of Wilms' tumor cells, whereas ADH1C overexpression offset the cancer-promoting influence of miR-135b-3p upregulation on Wilms' tumor progression. Therefore, LINC01339 prevents Wilms' tumor progression by modulating the miR-135b-3p/ADH1C axis. Our findings substantiate that the LINC01339/miR-135 b-3p/ADH1C regulatory axis has potential to be a target for the treatment of Wilms' tumor.

Functional implications of rs9373441 with FOXP3+Treg and Tr1 for the clinical effectiveness of csDMARDs in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by a deficiency in regulatory T cells (Treg), which play a crucial role in immune regulation. While conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are widely used, there remains a challenge as efficacy varies among patients. In this genome-wide association study (GWAS) involving 410 RA patients, rs9373441 emerged as the most significantly linked single-nucleotide polymorphism (SNP) to csDMARDs response. This non-coding variant functions as a cis-acting regulatory element within the UTRN gene, which is associated with cortical erosion and osteoporosis. Particularly, individuals with the TT allele at rs9373441 exhibited a more favorable response, characterized by a significant increase in FOXP3 + Treg and Type 1 regulatory T cells (Tr1) (p = 0.04, 0.02) and a decrease in Effector T helper cells (Effector Th) (p = 0.03). The GATA3-GCM2-PTH and GATA3-FOXO1-FOXP3 pathways were implicated. RNA-sequencing (RNA-seq) analysis revealed increased expression levels of UTRN, PTH2R, FOXO1, and FOXO3 in good and moderate responders (p = 0.01, 0.03, 0.0005, and 0.02). Notably, the change in FOXP3 + Treg and Tr1 was positively correlated with UTRN expression (both p = 0.03). These findings underscore the critical link between rs9373441 and the response to csDMARDs, empowering clinicians to tailor treatments for enhanced outcomes in patients with RA.

ORC1 binds to cis-transcribed RNAs for efficient activation of replication origins.

Cells must coordinate the activation of thousands of replication origins dispersed throughout their genome. Active transcription is known to favor the formation of mammalian origins, although the role that RNA plays in this process remains unclear. We show that the ORC1 subunit of the human Origin Recognition Complex interacts with RNAs transcribed from genes with origins in their transcription start sites (TSSs), displaying a positive correlation between RNA binding and origin activity. RNA depletion, or the use of ORC1 RNA-binding mutant, result in inefficient activation of proximal origins, linked to impaired ORC1 chromatin release. ORC1 RNA binding activity resides in its intrinsically disordered region, involved in intra- and inter-molecular interactions, regulation by phosphorylation, and phase-separation. We show that RNA binding favors ORC1 chromatin release, by regulating its phosphorylation and subsequent degradation. Our results unveil a non-coding function of RNA as a dynamic component of the chromatin, orchestrating the activation of replication origins.

Long Noncoding RNA SNHG6 Functions as a Competing Endogenous RNA by Sponging miR-181a-5p to Regulate E2F5 Expression in Colorectal Cancer [Retraction

[This retracts the article DOI: 10.2147/CMAR.S182719.].

HERV-W ENV Induces Innate Immune Activation and Neuronal Apoptosis via linc01930/cGAS Axis in Recent-Onset Schizophrenia.

Schizophrenia is a severe neuropsychiatric disorder affecting about 1% of individuals worldwide. Increased innate immune activation and neuronal apoptosis are common findings in schizophrenia. Interferon beta (IFN-β), an essential cytokine in promoting and regulating innate immune responses, causes neuronal apoptosis in vitro. However, the precise pathogenesis of schizophrenia is unknown. Recent studies indicate that a domesticated endogenous retroviral envelope glycoprotein of the W family (HERV-W ENV, also called ERVWE1 or syncytin 1), derived from the endogenous retrovirus group W member 1 (ERVWE1) locus on chromosome 7q21.2, has a high level in schizophrenia. Here, we found an increased serum IFN-β level in schizophrenia and showed a positive correlation with HERV-W ENV. In addition, serum long intergenic non-protein coding RNA 1930 (linc01930), decreased in schizophrenia, was negatively correlated with HERV-W ENV and IFN-β. In vitro experiments showed that linc01930, mainly in the nucleus and with noncoding functions, was repressed by HERV-W ENV through promoter activity suppression. Further studies indicated that HERV-W ENV increased IFN-β expression and neuronal apoptosis by restraining the expression of linc01930. Furthermore, HERV-W ENV enhanced cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes protein (STING) expression and interferon regulatory factor 3 (IRF3) phosphorylation in neuronal cells. Notably, cGAS interacted with HERV-W ENV and triggered IFN-β expression and neuronal apoptosis caused by HERV-W ENV. Moreover, Linc01930 participated in the increased neuronal apoptosis and expression level of cGAS and IFN-β induced by HERV-W ENV. To summarize, our results suggested that linc01930 and IFN-β might be novel potential blood-based biomarkers in schizophrenia. The totality of these results also showed that HERV-W ENV facilitated antiviral innate immune response, resulting in neuronal apoptosis through the linc01930/cGAS/STING pathway in schizophrenia. Due to its monoclonal antibody GNbAC1 application in clinical trials, we considered HERV-W ENV might be a reliable therapeutic choice for schizophrenia.

CRS: An online database of Capsicum annuum RNA-seq libraries

RNA sequencing (RNA-seq) technique plays an important role in the analyses of gene expression profiling, transcript variation, non-coding sequence function, and so on. RNA-seq technique has been widely used in Capsicum annuum (chili pepper) research. The number of current pepper RNA-seq libraries is huge and is increasing every year. It is not only difficult for researchers to obtain the underlying information of these data, but also causes a waste of resources to some extent. To solve this problem, we developed an online database, namely CRS, to host 467 publicly available RNA-seq libraries of C. annuum obtained from the Sequence Read Archive database (as of November 2021), which integrates the information of gene expression, tissue specificity, Gene Ontology terms, and KEGG Orthology. We believe that CRS will enable more convenient and efficient exploration of pepper RNA-seq data and be conducive to a deeper understanding of the pepper genome.

LncReader: identification of dual functional long noncoding RNAs using a multi-head self-attention mechanism

Long noncoding ribonucleic acids (RNAs; LncRNAs) endowed with both protein-coding and noncoding functions are referred to as 'dual functional lncRNAs'. Recently, dual functional lncRNAs have been intensively studied and identified as involved in various fundamental cellular processes. However, apart from time-consuming and cell-type-specific experiments, there is virtually no in silico method for predicting the identity of dual functional lncRNAs. Here, we developed a deep-learning model with a multi-head self-attention mechanism, LncReader, to identify dual functional lncRNAs. Our data demonstrated that LncReader showed multiple advantages compared to various classical machine learning methods using benchmark datasets from our previously reported cncRNAdb project. Moreover, to obtain independent in-house datasets for robust testing, mass spectrometry proteomics combined with RNA-seq and Ribo-seq were applied in four leukaemia cell lines, which further confirmed that LncReader achieved the best performance compared to other tools. Therefore, LncReader provides an accurate and practical tool that enables fast dual functional lncRNA identification.

Long Non-Coding RNA CASC2 Functions as A Tumor Suppressor in Colorectal Cancer via Modulating The miR-18a-5p/BTG3 Pathway.

Reportedly, long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is involved in regulating colorectal cancer (CRC) progression. However, the function and detailed downstream mechanism of CASC2 in CRC progression are not fully elucidated. The aim of the study was to investigate the potential function and molecular mechanism of CASC2 in CRC progression. In this experimental study, quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to probe CASC2, microRNA-18a-5p (miR-18a-5p) and B cell translocation gene 3 (BTG3) mRNA expression in CRC tissues and cell lines. After CASC2 was overexpressed in Colo-678 and HCT116 cell lines, methylthiazol tetrazolium (MTT) and 5-bromo-2'-deoxyuridine (BrdU) assays were employed to examine the proliferation of CRC cells. Transwell migration and invasion assays were executed to evaluate the metastatic potential of CRC cells. The targeting relationships among CASC2, miR-18a-5p and BTG3 were validated by dual luciferase reporter gene assay. Western blot assay was applied to examine the regulatory effects of CASC2 and miR-18a-5p on BTG3 protein expression. CASC2 was decreased in CRC tissues and cell lines, and its low expression in CRC tissues was associated with larger tumor size and lymph node metastasis. CASC2 overexpression restrained proliferative, migrative and invasive capabilities of CRC cells. CASC2 could function as a molecular sponge for miR-18a-5p and repress the expression of miR-18a-5p. Furthermore, the inhibitory effects of CASC2 on the malignant phenotypes of CRC cells was counteracted by miR-18a-5p mimics. Additionally, CASC2 could positively regulate BTG3 expression via suppressing miR-18a-5p. CASC2 inhibits CRC development by suppressing miR-18a-5p and raising BTG3 expression.

Cardiomyocyte-Specific Long Noncoding RNA Regulates Alternative Splicing of the Triadin Gene in the Heart.

Abnormalities in Ca2+ homeostasis are associated with cardiac arrhythmias and heart failure. Triadin plays an important role in Ca2+ homeostasis in cardiomyocytes. Alternative splicing of a single triadin gene produces multiple triadin isoforms. The cardiac-predominant isoform, mouse MT-1 or human Trisk32, is encoded by triadin exons 1 to 8. In humans, mutations in the triadin gene that lead to a reduction in Trisk32 levels in the heart can cause cardiac dysfunction and arrhythmias. Decreased levels of Trisk32 in the heart are also common in patients with heart failure. However, mechanisms that maintain triadin isoform composition in the heart remain elusive. We analyzed triadin expression in heart explants from patients with heart failure and cardiac arrhythmias and in hearts from mice carrying a knockout allele for Trdn-as, a cardiomyocyte-specific long noncoding RNA encoded by the antisense strand of the triadin gene, between exons 9 and 11. Catecholamine challenge with isoproterenol was performed on Trdn-as knockout mice to assess the role of Trdn-as in cardiac arrhythmogenesis, as assessed by ECG. Ca2+ transients in adult mouse cardiomyocytes were measured with the IonOptix platform or the GCaMP system. Biochemistry assays, single-molecule fluorescence in situ hybridization, subcellular localization imaging, RNA sequencing, and molecular rescue assays were used to investigate the mechanisms by which Trdn-as regulates cardiac function and triadin levels in the heart. We report that Trdn-as maintains cardiac function, at least in part, by regulating alternative splicing of the triadin gene. Knockout of Trdn-as in mice downregulates cardiac triadin, impairs Ca2+ handling, and causes premature death. Trdn-as knockout mice are susceptible to cardiac arrhythmias in response to catecholamine challenge. Normalization of cardiac triadin levels in Trdn-as knockout cardiomyocytes is sufficient to restore Ca2+ handling. Last, Trdn-as colocalizes and interacts with serine/arginine splicing factors in cardiomyocyte nuclei and is essential for efficient recruitment of splicing factors to triadin precursor mRNA. These findings reveal regulation of alternative splicing as a novel mechanism by which a long noncoding RNA controls cardiac function. This study indicates potential therapeutics for heart disease by targeting the long noncoding RNA or pathways regulating alternative splicing.

Sympatric Speciation in Mole Rats and Wild Barley and Their Genome Repeatome Evolution: A Commentary.

The theories of sympatric speciation (SS) and coding and noncoding (cd and ncd =repeatome) genome function are still contentious. Studies on SS in our two new models, "Evolution Canyon" and "Evolution Plateau", in Israel, divergent microclimatically and geologically-edaphically, respectively, indicated that in ecologically divergent microsites SS is a common speciation model across life from bacteria to mammals. Genomically, the intergenic ncd repeatome was and is still regarded by many biologists as "selfish," "junk," and non-functional. In contrast, it is considered by the encyclopedia of DNA elements discovery as biochemically functional and regulatory, and the transposable elements were considered earlier by Barbara McClintock as "controlling elements" of genes. Remarkably, it is found that repeated elements can statistically identify significantly, the five species of subterranean mole rats of Spalax ehrenbergi superspecies adapted to increasingly arid climatic trend southward in Israel. Moreover, it is first discovered in the SS studies in two distant taxa, subterranean mole rats and wild barley, and later also in spiny mice in Israel and subterranean zokors in China, that the noncoding repeatome is genomically mirroring the image of the protein-coding genome in divergent ecologies. It is shown that this mirroring image is statistically significant both within and between the ecologically divergent taxa supporting the hypothesis that much of the repeatome might be regulatory and selected as the protein-coding genome by the same ecological stresses.

Long Non-Coding RNA LINC00239 Functions as a Competitive Endogenous RNA by Sponging microRNA-484 and Enhancing KLF12 Expression to Promote the Oncogenicity of Colorectal Cancer [Retraction

[This retracts the article DOI: 10.2147/OTT.S278582.].

Circ_0022340 promotes colorectal cancer progression via HNRNPC/EBF1/SYT7 or miR-382-5p/ELK1 axis

Circular RNAs (circRNAs) are characterized as a class of new noncoding RNAs and function in tumorigenesis of colorectal cancer (CRC). In our study, the molecule mechanism of circ_0022340 in CRC was investigated. For this aim, quantitative real-time polymerase chain reaction (RT-qPCR) was used to test gene expression in CRC cells. Cell function assays including 5-ethynyl-20-deoxyuridine (EdU), colony formation and transwell investigated the proliferation and migration capacity in CRC cells. Luciferase reporter and RNA immunoprecipitation (RIP)assays determined the interaction between circRNA, miRNA and mRNA. Western blot was used to test protein expression. An immunohistochemistry assay was used to assess the tumor growth in vivo. Results showed that Circ_0022340 was highly expressed in CRC cells. Circ_0022340 was formed from exon 5 to 6 of the synaptotagmin 7 (SYT7). Silencing of circ_0022340 suppressed CRC cell proliferation and migration. Functionally, circ_0022340 recruited heterogeneous nuclear ribonucleoprotein C (HNRNPC) to stabilize EBF1 mRNA and thereby activated SYT7. Moreover, circ_0022340 targeted miR-382-5p to up-regulate ETS transcription factor ELK1 (ELK1). It is concluded that Circ_0022340 promoted colorectal cancer progression via recruiting HNRNPC to stabilize EBF1 mRNA and thereby activated SYT7 or miR-382-5p/ELK1 axis, which might provide a novel target for CRC treatment.

Isha is a su(Hw) mRNA-binding protein required for gypsy insulator function.

Chromatin insulators are DNA-protein complexes localized throughout the genome capable of establishing independent transcriptional domains. It was previously reported that the Drosophila su(Hw) mRNA physically associates with the gypsy chromatin insulator protein complex within the nucleus and may serve a noncoding function to affect insulator activity. However, how this mRNA is recruited to the gypsy complex is not known. Here, we utilized RNA-affinity pulldown coupled with mass spectrometry to identify a novel RNA-binding protein, Isha (CG4266), that associates with su(Hw) mRNA in vitro and in vivo. Isha harbors a conserved RNA recognition motif and RNA Polymerase II C-terminal domain-interacting domain (CID). We found that Isha physically interacts with total and elongating Polymerase II and associates with chromatin at the 5' end of genes in an RNA-dependent manner. Furthermore, ChIP-seq analysis reveals Isha overlaps particularly with the core gypsy insulator component CP190 on chromatin. Depletion of Isha reduces enhancer-blocking and barrier activities of the gypsy insulator and disrupts the nuclear localization of insulator bodies. Our results reveal a novel factor Isha that promotes gypsy insulator activity that may act as a nuclear RNA-binding protein adapter for su(Hw) noncoding mRNA.

Long Non-Coding RNA RFPL3S Functions as a Biomarker of Prognostic and Immunotherapeutic Prediction in Testicular Germ Cell Tumor.

The incidence of testicular germ cell tumor (TGCT) is currently on the rise worldwide, of which 15%-30% of patients have occur recurrence and metastasis. However, clinical methods for diagnosing TGCT and judging its prognosis remained inadequate. In this study, we aimed to explore the possibility of testis-specific long-chain non-coding RNA (lncRNA) Ret finger protein-like 3S (RFPL3S) as a biomarker for TGCT diagnosis, prognosis, and treatment response by reviewing the TGCT gene expression data in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The cohort data and DNA methylation data of TGCT in TCGA were downloaded from TGCA, UCSC XENA, and GEO. The bioinformatic tools were used, including GEPIA2, Kaplan-Meier Plotter, LinkedOmics, UCSC XENA, Sangerbox Tools, GSCA, and Tumor Immune Dysfunction and Exclusion. Compared with normal testicular tissues, the RFPL3S expression was significantly reduced in TGCT, and was significantly negatively correlated with the patient’s Tumor, Node, Metastasis stage. Hypermethylation and low copy number of RFPL3S were present in TGCT, and low RFPL3S was associated with short disease-free and progression-free intervals. Silencing RFPL3S significantly enhanced the invasion ability and proliferation ability of TGCT cells as evaluated by Transwell and CCK-8 experiments. Additionally, RFPL3S expression was positively correlated with the infiltration of immune-activating cells such as B cells, CD8+ T cells, cytotoxic T cells, and natural killer cells, and negatively correlated with the infiltration of immunosuppressive cells such as Th17 and Th2. Higher RFPL3S expression was present in patients with immunotherapy benefits. In conclusion, we determined that the testis-specific lncRNA RFPL3S functioned as a tumor suppressor in TGCT and could be used as a prognostic predictor of TGCT, as well as a marker to predict the effect of TGCT immunotherapy.

Circular RNAs Acting as miRNAs' Sponges and Their Roles in Stem Cells.

Circular RNAs (circRNAs), a novel type of endogenous RNAs, have become a subject of intensive research. It has been found that circRNAs are important players in cell differentiation and tissue homeostasis, as well as disease development. Moreover, the expression of circRNAs is usually not correlated with their parental gene expression, indicating that they are not only a steady-state by-product of mRNA splicing but a product of variable splicing under novel regulation. Sequence conservation analysis has also demonstrated that circRNAs have important non-coding functions. CircRNAs exist as a covalently closed loop form in mammalian cells, where they regulate cellular transcription and translation processes. CircRNAs are built from pre-messenger RNAs, and their biogenesis involves back-splicing, which is catalyzed by spliceosomes. The splicing reaction gives rise to three different types of intronic, exotic and exon–intron circular RNAs. Due to higher nuclease stability and longer half lives in cells, circRNAs are more stable than linear RNAs and have enormous clinical advantage for use as diagnostic and therapeutic biomarkers for disease. In recent years, it has been reported that circRNAs in stem cells play a crucial role in stem cell function. In this article, we reviewed the general feature of circRNAs and the distinct roles of circRNAs in stem cell biology, including regulation of stem cell self-renewal and differentiation. CircRNAs have shown unique expression profiles during differentiation of stem cells and could serve as promising biomarkers of these cells. As circRNAs play pivotal roles in stem cell regulation as well as the development and progression of various diseases, we also discuss opportunities and challenges of circRNA-based treatment strategies in future effective therapies for promising clinical applications.

Retraction notice to Long Noncoding RNA LINC01133 Functions as an miR-422a Sponge to Aggravate the Tumorigenesis of Human Osteosarcoma [Oncology Research 26(3) (2018) 335343

Retraction notice to Long Noncoding RNA LINC01133 Functions as an miR-422a Sponge to Aggravate the Tumorigenesis of Human Osteosarcoma [Oncology Research 26(3) (2018) 335343